Minipuberty period of children with atopic dermatitis compared to healthy children.

Background/aim: Atopic dermatitis (AD) is an inflammatory, pruritic, noncontagious, chronic relapsing skin disease. Skin barrier abnormalities, excessive T helper 2 activity, and immune dysregulation are held responsible. Androgens have a negative effect on the integrity of the epidermal skin barrier, while estrogen has a positive effect. We aimed to investigate whether hormones make a difference between healthy children and children with AD during minipuberty. Materials and methods: A total of 96 infants (postnatal 4-13 weeks), 48 diagnosed with AD and 48 controls, were included. Each group consisted of 23 girls (47.9%) and 25 boys (52.1%). Anthropometric examinations and hormone measurements were compared. Results: The two groups, having similar age, sex, body mass index, and weight-for-length standard deviation scores, were compared. Serum free thyroxine (FT4) levels were found to be lower and insulin-like growth factor binding protein-3 (IGFBP3) levels were found to be higher in children with AD (p < 0.001 and p = 0.038, respectively). In girls with AD, estradiol, FT4, and insulin-like growth factor-1 (IGF-1) levels were found to be lower, but thyroid-stimulating hormone (TSH) levels were found to be higher (p = 0.023, p < 0.001, p = 0.038, and p = 0.034, respectively). In boys with AD, the FT4 level was found to be lower (p = 0.023). Serum FT4 and TSH levels were within normal reference ranges in all comparisons. Conclusion: Especially in girls with AD, decreased estradiol and IGF-1 levels were observed compared to the controls during minipuberty. In the logistic regression model, decreased levels of serum estradiol, dehydroepiandrosterone sulfate, FT4, and IGF-1, and increased levels of IGFBP3 were associated with an increased likelihood of exhibiting atopic dermatitis.

A Novel Biallelic LCK Variant Resulting in Profound T-Cell Immune Deficiency and Review of the Literature.

Lymphocyte-specific protein tyrosine kinase (LCK) is an SRC-family kinase critical for initiation and propagation of T-cell antigen receptor (TCR) signaling through phosphorylation of TCR-associated CD3 chains and recruited downstream molecules. Until now, only one case of profound T-cell immune deficiency with complete LCK deficiency [1] caused by a biallelic missense mutation (c.1022T>C, p.L341P) and three cases of incomplete LCK deficiency [2] caused by a biallelic splice site mutation (c.188-2A>G) have been described. Additionally, deregulated LCK expression has been associated with genetically undefined immune deficiencies and hematological malignancies. Here, we describe the second case of complete LCK deficiency in a 6-month-old girl born to consanguineous parents presenting with profound T-cell immune deficiency. Whole exome sequencing (WES) revealed a novel pathogenic biallelic missense mutation in LCK (c.1393T>C, p.C465R), which led to the absence of LCK protein expression and phosphorylation, and a consecutive decrease in proximal TCR signaling. Loss of conventional CD4+ and CD8+ αßT-cells and homeostatic T-cell expansion was accompanied by increased γδT-cell and Treg percentages. Surface CD4 and CD8 co-receptor expression was reduced in the patient T-cells, while the heterozygous mother had impaired CD4 and CD8 surface expression to a lesser extent. We conclude that complete LCK deficiency is characterized by profound T-cell immune deficiency, reduced CD4 and CD8 surface expression, and a characteristic TCR signaling disorder. CD4 and CD8 surface expression may be of value for early detection of mono- and/or biallelic LCK deficiency.

Neonatal Lymphopenia Screening Is Important for Early Diagnosis of Severe Combined Immunodeficiency.

OBJECTIVE: T-cell receptor excision circles are expensive for neonatal severe combined immunodeficiency screening in developing countries. We aimed to detect immunodeficiencies presenting with lymphopenia to enable screening in the general population and to improve awareness regarding lymphopenia among clinicians. STUDY DESIGN: This study was conducted prospectively. In all newborns included, complete blood count from umbilical cord blood samples was recorded. Absolute lymphopenia was defined as absolute lymphocyte count <3,000/mm3 in umbilical cord blood sample. Complete blood count was repeated at month 1 in cases found to have lymphopenia. RESULTS: Overall, 2,000 newborns were included in the study. Absolute lymphopenia was detected in 42 newborns (2.1%), while lymphocyte count was >3,000/mm3 in 1,958 newborns (97.9%). Two infants with persisted lymphopenia at the end of the first month; therefore, further evaluations such as lymphocyte subsets for severe combined immunodeficiency (SCID) were done. In the first infant, the lymphocyte subgroups were detected as compatible with T (-), B (-), natural killer cells (NK) (+) SCID phenotype RAG defect. Sanger sequencing revealed that NM_000448 c.2209C > T (p.R737C) homozygous mutation of RAG1 gene. In the other infant, the lymphocyte subgroups were found as considered with T (-), B (+) NK (-) SCID phenotype JAK3 defect. Both patients underwent hematopoietic stem cell transplantation from human leukocyte antigen-matched family member. CONCLUSION: Absolute lymphopenia by complete blood count is a more simpler, relatively noninvasive and inexpensive screening methodfor detection of SCID in newborns compared with T-cell receptor excision circles technique. KEY POINTS: · Our study was conducted with a much smaller number of study groups compared with the previous ones.. · However, SCID was found at a higher rate compared with other studies.. · Our study for this disease that is common in our country where consanguineous marriages are common.

Comparing the levels of CTLA-4-dependent biological defects in patients with LRBA deficiency and CTLA-4 insufficiency.

BACKGROUND: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency. METHODS: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (TFH ), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation. RESULTS: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cTFH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cTFH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%). CONCLUSION: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway.

Common Variable Immunodeficiency, Autoimmune Hemolytic Anemia, and Pancytopenia Associated With a Defect in IKAROS.

OBJECTIVE: Mutations in IKZF1, which encodes Ikaros family zinc finger 1 (IKAROS) transcription factor, are associated with recurrent infections, cytopenia, autoimmune diseases, and hematologic malignancies. Diverse clinical phenotypes resulting from IKZF1 mutations include pulmonary fungal infections, cytopenia, autoimmune hemolytic anemia (AIHA), and malignancies. In this study, we aimed to assess the DNA-binding ability and pericentromeric (PC) localization of a variant of IKZF discovered in a patient. MATERIALS AND METHODS: DNA-binding ability of a pathogenic IKZF variant was tested using electrophoretic mobility shift assay and PC localization of the variant was assessed by immunofluorescent microscopy in NIH3T3 cells. RESULTS: Clinical features of a 3-month-old male infant who underwent hematopoietic stem cell transplantation because of an IKZF1 mutation-associated common variable immunodeficiency, AIHA, and pancytopenia are described. DNA studies revealed a heterozygous missense variant (IKZF1 NM_006060 c.427C>T; p.R143W). Cotransfection studies revealed that mutant R143W has a partial dominant-negative effect over PC targeting and DNA binding. CONCLUSIONS: IKZF1 mutation must be kept in mind if neonatal AIHA, common variable immunodeficiency, and pancytopenia are observed.

What plays a role in the severity of atopic dermatitis in children?

Background/aim: Determining the characteristics and risk factors of severe disease is extremely important to combat atopic dermatitis (AD), which has recently shown increasing prevalence. In this study, we aimed to investigate the clinical characteristics of pediatric patients with AD and identifying the factors associated with the severity of the disease. Materials and methods: A total of 304 pediatric patients diagnosed with atopic dermatitis were included in the study. The patients' age at admission, age at onset of symptoms, the presence of atopy history in their family, eosinophil levels obtained from blood counts were recorded, together with the data of cigarette exposure, and area of residence. Disease severity was determined according to the SCORAD index. Epidermal prick tests (EPT) were applied to all patients. Results: There was a negative correlation between the SCORAD score and both age at admission (r = 0.277, p < 0.001) and age at onset of the symptoms (r = ­0.474, p < 0.001). Food sensitization rates were higher in individuals with moderate-severe disease (90.7% vs. 23.1%; p < 0.001) and patients with food allergy (FA) had significantly higher SCORAD scores [33 (IQR: 22­44) vs. 14 (IQR: 12­16); p < 0.001]. SCORAD scores of the individuals living in rural areas were higher than the ones living in urban [22 (IQR: 15­39.5) vs. 15 (IQR: 12­22); p < 0.001]. Familial atopy history was more common in patients with moderate-severe disease (66.5% vs. 17.5%; p < 0.001). The SCORAD scores were higher in patients exposed to passive smoking [21 (IQR:14.75­38) vs. 13 (IQR: 12­16); p < 0.001]. The eosinophil count found to be positively correlated with SCORAD scores (r = 0.531, p < 0.001). Conclusion: Our findings show that early-onset, food sensitivity, living in rural areas, having familial atopy history and passive cigarette smoke exposure play a role in severe AD. Since it is remarkably correlated with SCORAD scores, eosinophil count can be used as a marker to assess the severity of AD in children.

ILC3 deficiency and generalized ILC abnormalities in DOCK8-deficient patients.

BACKGROUND: Dedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans. METHODS: Peripheral blood ILC1-3 subsets of 16 DOCK8-deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post-transplant DOCK8-deficient patients (n = 12) by flow cytometry and real-time qPCR. Sorted total ILCs from DOCK8- or STAT3-mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL-7, IL-23, and IL-12 by cell culture, flow cytometry, and phospho-flow assays. RESULTS: DOCK8-deficient but not STAT3-mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8-deficient ILC1-3 subsets had defective proliferation, expressed lower levels of IL-7R, responded less to IL-7, IL-12, or IL-23 cytokines, and were more prone to apoptosis compared with those of healthy controls. CONCLUSION: DOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8-deficient patients to infections.

A Rare Case of Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Presenting With Hemophagocytosis Complicated With Hodgkin Lymphoma.

Gain of function mutations in the p110δ catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) classified as activated phosphoinositide 3-kinase delta syndrome (APDS) are the cause of a primary immunodeficiency characterized by recurrent sinopulmonary infections, and lymphoproliferation. Previously, autoimmunity and Epstein-Barr virus-related B-cell lymphoma have been documented for patients with APDS; here, we present a case that extends the picture, as the patient shows the full diagnostic criteria of hemophagocytic lymphohistiocytosis at 6 months of age. He experienced Hodgkin lymphoma as a 2.5-year-old baby. Next-generation sequencing returned a de novo heterozygous missense variant in PIK3CD (LRG_191t1: c.3061G>A; p.Glu1021Lys), confirming the primary immunodeficiency. After 2 courses of ifosfamide, cisplatin, and etoposide combined with brentuximab, the patient successfully underwent allogeneic hematopoietic stem cell transplantation from his HLA full matched sister, and he has been well for 18 months after that. The hematologist treating Hodgkin lymphoma and/or hemophagocytic lymphohistiocytosis should be vigilant about the possible underlying immune deficiency, and they should consider APDS in their differential diagnosis.

Genetic Deficiency and Biochemical Inhibition of ITK Affect Human Th17, Treg, and Innate Lymphoid Cells.

PURPOSE: Interleukin-2-inducible T cell kinase (ITK) is an important mediator of T cell receptor signaling. Loss of function mutations in ITK results in hypogammaglobulinemia and CD4+ T cell loss in humans, and the patients often present with EBV-associated B cell lymphoproliferative syndrome. Itk-deficient mice show loss of T cell naivety, impaired cytolytic activity of CD8+ T cells, and defects in CD4+ T cell lineage choice decisions. In mice, Itk mutations were shown to affect Th17-Treg lineage choice in favor of the latter. In this study, we explored whether human ITK reciprocally regulates Th17-Treg balance as its murine ortholog. METHODS: Whole Exome Sequencing was used to identify the mutation. ITK-deficient peripheral blood lymphocytes were characterized by FACSAria III-based flow cytometric assays with respect to proliferation, apoptosis, cytokine production, and innate lymphoid cell (ILC) frequency. Sorted T cells from healthy donors were exposed to ibrutinib, an irreversible ITK inhibitor, to assess ITK's contribution to Th17 and Treg cell generation and functions. RESULTS: In this study, we report a child with a novel ITK mutation who showed impaired CD3/CD28 induced proliferation in T cells. ITK-mutant cells were more apoptotic irrespective of TCR activation. More importantly, T cells produced less Th17-associated cytokines IL-17A, IL-22, and GM-CSF. Conversely, Th1-associated IFN-γ production was increased. An irreversible inhibitor of ITK, ibrutinib, blocked ex vivo Th17 generation and IL-17A production, conversely augmented FOXP3 expression only at low doses in Treg cultures. Finally, we analyzed peripheral ILC populations and observed a relative decrease in ILC2 and ILC3 frequency in our ITK-deficient patient. CONCLUSIONS: To our knowledge, this is the first report showing that both genetic and chemical inhibition of ITK result in reduced Th17 generation and function in humans. We also report, for the first time, a reduction in ILC2 and ILC3 populations in an ITK-deficient human patient.

Early Retinal Findings Following Cooling in Neonatal Encephalopathy.

BACKGROUND AND AIM: Perinatal HI (hypoxia-ischemia)-related visual defects including blindness are known to be associated with ischemic lesions in intracerebral visual pathways and ischemic retinal damage (IRD). Intraocular hemorrhages (IOH) such as retinal hemorrhage (RH), which may result from perinatal HI, can cause IRD by various mechanisms. We aimed to evaluate the early retinal findings in neonates with moderate-to-severe neonatal encephalopathy (NE) who underwent TH and its relationship between coagulation status, amplitude-integrated electroencephalography (aEEG) patterns, and magnetic resonance imaging-magnetic resonance spectroscopy (MRI-MRS) findings. METHOD AND PATIENTS: A total of 31 newborn infants who underwent moderate-to-severe NE and TH included in the study. Coagulation parameters were taken immediately before starting TH, and daily during TH period. aEEG records were obtained during TH and rewarming period.Binocular indirect ophthalmoscopic examination (BIOE) and MRI-MRS scanning were performed when TH protocol completed. RESULTS: Total 13 (41.9%) patients had abnormal BIOE findings. Ten of them were (77%) IOH, other findings are as follows: RH (n = 7), optic disc hemorrhage (n = 2), and vitreous hemorrhage (n = 1). Initial coagulation status was not related to IOH. Worsened aEEG and MRI-MRS results were not related to BIOE findings. CONCLUSION: Frequency of IOH is high in newborns with NE who underwent TH being independent from severity of MRS-MRI findings, aEEG pattern, and disturbed coagulation status.

Correction to: Novel Mutations in RASGRP1 Are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma.

The original version of this article unfortunately contained mistakes in Author's name, in Table 1 and in result section.

Novel Mutations in RASGRP1 are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma.

PURPOSE: RAS guanyl-releasing protein 1 (RASGRP1) deficiency has recently been shown to cause a primary immunodeficiency (PID) characterized by CD4+ T cell lymphopenia and Epstein-Barr virus (EBV)-associated B cell lymphoma. Our report of three novel patients widens the scope of RASGRP1 deficiency by providing new clinical and immunological insights on autoimmunity, immune cell development, and predisposition to lymphoproliferative disease. METHODS: One patient of Turkish origin (P1) and two Palestinian patients (P2, P3) were evaluated for immunodeficiency. To decipher the molecular cause of disease, whole exome sequencing was conducted. Identified mutations were validated by immunological and biochemical assays. RESULTS: We report three patients presenting with similar clinical characteristics of immunodeficiency and EBV-associated lymphoproliferative disease. In addition, P2 and P3 exhibited overt autoimmune manifestations. Genetic screening identified two novel loss-of-function mutations in RASGRP1. Immunoblotting and active Ras pull-down assays confirmed perturbed ERK1/2 signaling and reduced Ras-GTPase activity in heterologous Jurkat cells with ectopic expression of RASGRP1 mutants. All three patients had CD4+ T cell lymphopenia. P2 and P3 showed decreased mitogen-induced lymphocyte proliferation, reduced T cell receptor excision circles, abnormal T cell receptor (TCR) Vß repertoires, and increased frequencies of TCRγδ cells. TCR gamma repertoire diversity was significantly reduced with a remarkable clonal expansion. CONCLUSIONS: RASGRP1 deficiency is associated with life-threatening immune dysregulation, severe autoimmune manifestations, and susceptibility to EBV-induced B cell malignancies. Early diagnosis is critical and hematopoietic stem cell transplantation might be considered as curative treatment.

Evaluation of clinical and demographic features of childhood food allergy: A single-center experience.

OBJECTIVE: Current evaluations of pediatric food allergies are very important, many studies have shown that the frequency of food allergies is increasing in the pediatric age group. In this study, we retrospectively investigated the epidemiology and clinical features to better understand the clinical effects of food allergy, to contribute to the literature on this subject, and to evaluate the data of our country. METHODS: The epidemiological and clinical data of patients with food allergies diagnosed at the Erciyes University Pediatric Allergy Outpatient Clinic between 2014 and 2019 were analyzed. The outcomes were analyzed by a statistical analyzing program and compared with the literature. RESULTS: As a result of our retrospective evaluation, we found that the mean age of 854 patients who were diagnosed with food allergy was 21.2±30.7 months (min 0 months, max 16.5 years). 512 (60%) of our patients were female, and 342 (40%) were male. The most common complaint was rash at the rate of 75.2% and followed by itching 27.6%, angioedema 10.5%, bloody defecation 10.5%, wheezing 8.4%, vomiting 8.3%, diarrhea 6.7%, frequent bronchiolitis 6.6%, cough 6.2%, and shortness of breath 4.4%. It was shown that 32.2% of the patient had multiple food allergies and the highest sensitivity rates were 65.9% with egg allergies and 39.2% with milk. In the classification, it was found that 75.1% of the patients who were followed up with food allergy had IgE-mediated food allergy, and 24.9% had a non-IgE-mediated food allergy. CONCLUSION: The results of this study of a 5-year cross-sectional evaluation of the patients diagnosed with food allergy and followed up in our clinic may contribute to the growing body of literature on pediatric-age food allergy.

Comparison of 25-OH vitamin D levels between children with upper and those with lower extremity fractures: A prospective case-control study.

OBJECTIVE: The aims of this study were (1) to compare 25-OH vitamin D levels between children with upper and those with lower extremity fractures and (2) to determine whether 25-OH D insufficiency prevalence is increased compared to healthy controls. METHODS: This is a prospective case-control study for 12 months. The study was conducted with children aged 5-18 years, including 60 children with non-displaced, impaction type upper extremity and lower extremity fractures resulted from low-energy trauma. In addition, 60 healthy children were included as controls. In all participants, risk factors for low bone mineral density were assessed and serum 25(OH)D levels were measured. Vitamin D levels were compared among groups. RESULTS: Vitamin D deficiency (25-OH D <20) was 14.8 times (OR= 95% CI= 5.61 - 39.8) and 2.9 times (OR= 95% CI= 1.46-5.75) higher in patients with upper and lower extremity fractures, respectively. In the upper extremity fracture group, serum 25-OH D level was considered deficient (25-OH D level=<20 ng/mL) in 91.6% (55/60). In comparison, it was considered as insufficient (serum 25-OH D level=20-30 ng/mL in 8.3% (5/60) of the patients. In the lower extremity fracture group, serum 25(OH)D level was considered as deficient in 75.0% (45/60), while it was considered as insufficient in 25.0% (15/60) of the patients. In the control group, serum 25-OH D level was considered deficient in 10.0% (6/60), while it was considered insufficient in 61.6% (37/60) of subjects. The 25-OH D deficiency and insufficiency were more common in the whole fracture group (upper plus lower extremity fracture groups) when compared to healthy controls. CONCLUSION: This study has shown that hypovitaminosis D is associated with an increased risk for fracture in the pediatric population, and the fracture risk is higher in upper extremity fractures than in lower extremity fractures. In children with fractures, routine vitamin D evaluation should be considered. LEVEL OF EVIDENCE: Level III, Diagnostic Study.

The association of allergic rhinitis severity with neutrophil-lymphocyte and platelet-lymphocyte ratio in children.

OBJECTIVE: The aim of the study was to investigate the relationship between the severity of allergic rhinitis (AR) and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in pediatric patients. METHODS: This study is a retrospective, cross-sectional, and observational study including 200 AR patients and 160 healthy controls. Of the patients, 39% were boys with a mean age of 10.5 years. The study included children with persistent and intermittent AR. Of the controls, 50.6% were boys with a mean age of 10.3 years. We compared NLR and PLR from blood test between study and control groups. They were also compared according to AR severity within the patient group. RESULTS: The NLR was 1.64±1.29 in the study group whereas 1.18±0.31 in the control group. The PLR was 102.72±31.20 in the study group whereas 79.36±11.72 in the control group. When NLR and PLR were compared between groups, we found statistically significant differences in both NLR and PLR (p=0.003, p=0.001, respectively). We found a statistically significant difference when comparing both NLR and PLR in patients with intermittent and persistent AR. These rates increased with disease severity (p=0.000, p=0.000, respectively). CONCLUSION: Both NLR and PLR are useful markers for the diagnosis and severity of AR. Clinicians can use these markers to assess disease severity in pediatric patients at the beginning of the diagnostic process.

Serum levels of soluble HLA-G correlate with disease activity in pediatric patients with Crohn's disease.

Background: Human leukocyte antigen (HLA)-G, a member of the HLA family, is crucial for fetomaternal tolerance. Transmembrane or circulating/soluble HLA-G (sHLA-G) is elevated in autoimmune conditions and the tumor microenvironment. Circulating sHLA-G levels and their association with disease activity have not yet been assessed in pediatric patients with inflammatory bowel disease (IBD). This study aimed to quantify the serum sHLA-G levels of pediatric patients with IBD and assess the association of serum sHLA-G with disease activity. Methods: : We enrolled 24 pediatric IBD patients Crohn's disease (CD) and ulcerative colitis (UC), n = 12 each] and 24 healthy controls. Based on the disease activity index, five and seven of the CD patients had mild and moderate/severe disease, respectively, whereas six of the UC patients were in remission and six had mild disease. Serum was collected and sHLA-G levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: : Pediatric patients with CD had significantly higher sHLA-G levels compared with patients with UC and healthy controls. Notably, serum sHLA-G levels were significantly higher in patients with moderate/severe CD than in those with mild CD. Conclusions: : Serum sHLA-G levels correlate with disease activity in pediatric patients with CD and are higher in CD patients than in UC patients. Thus, sHLA-G is a potential biomarker for disease activity in CD.

Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.

Underlying factors of recurrent infections in patients with down syndrome.

Down syndrome is the most common chromosomal aberration. Patientswith Down syndrome suffer more infections than those without the disease. Underlying immunological disorders are consideredto be the reason for the increasing frequency of infections in patients with Down syndrome. In addition, some anatomical abnormalities in the respiratory tractaccompanying Down syndrome can disturb the innate immunity and contribute to the increase in infection rate. Respiratory tract infections are one of the most common causes of mortality in patients with Down syndrome. Awareness of the underlying reason for frequent respiratory tract infections should result in a decrease in mortality among these patients and contribute to an improvementin their quality of life.